1. Technical Field
The present invention relates to an ion trap mass spectrometer comprising an ion trap operable to confine ions therein by an action of a high-frequency electric field.
2. Description of the Related Art
In late years, an ion trap mass spectrometer utilizing a three-dimensional quadrupole ion trap has been widely used as a highly-sensitive mass spectrometer. Typically, the three-dimensional quadrupole ion trap comprises one ring electrode having an inner surface in the shape of a hyperboloid of revolution of one sheet, and a pair of endcap electrodes disposed in opposed relation to each other across the ring electrode to have inner surfaces in the shape of a hyperboloid of revolution of two sheets.
In addition to the above ion trap, a basic configuration of the ion trap mass spectrometer includes an ion source operable to ionize a target substance to be measured, an ion transport optical system operable to transport ions produced by the ion source and introduce them into the ion trap, and an ion detector operable to detect each ion, wherein ions produced by the ion source are transported and introduced into the ion trap by the ion transport optical system to trap the ions, whereafter only a part of the ions having a specific mass are excited in a sequential manner so as to separate the ions depending on their masses, and the mass-separated ions are discharged from the ion trap and introduced to the ion detector so as to be subjected to detection. Alternatively, the mass spectrometer may be configured such that the ion trap is used for temporarily accumulating ions (or for fragmenting ions, on a case-by-case basis), instead of being used for the mass separation, and various ions concurrently discharged from the ion trap are introduced to a time-of-flight mass spectrometer to perform mass separation therein, whereafter the mass-separated ions are subjected to detection. Although this configuration is generally referred to as “ion trap time-of-flight mass spectrometer (IT-TOFMS)”, such a configuration is intended to be also covered by the term “ion trap mass spectrometer” as used in this specification.
In the above ion trap mass spectrometer, when the ion source is placed in a vacuum atmosphere, ions are transported to a mass separation/detection section in a subsequent stage, using an electrostatic ion transport optical system, such as an Einzel lens. Differently, when the ion source is placed in an atmospheric-pressure atmosphere or a low-vacuum atmosphere, the ions are transported to the mass separation/detection section, using a high-frequency electric field-based ion transport optical system, such as a high-frequency ion lens, while employing the configuration of a differential pumping system, because the mass separation/detection section is typically placed in a high-vacuum atmosphere.
The typical conventional ion trap is configured to apply a sine-wave high-frequency voltage to the ring electrode to form a trapping high-frequency electric field in a space surrounded by the electrodes, so that ions are confined therein while being oscillated by the high-frequency electric field. In this connection, a digital ion trap (DIT) has been recently developed, wherein a rectangular-wave voltage is applied to the ring electrode, in place of the sine-wave voltage, to perform ion confinement (see, for example, the following Patent Document 1 and Non-Patent Document 1).
In the conventional analog-type ion trap of the former, an LC resonator is used for generating a sine-wave high-frequency voltage, and the amplitude of the voltage is changed to control a mass range of trappable ions. In the digital-type ion trap of the latter, a DC voltage is switched at a high speed to generate a rectangular-wave high-frequency voltage, and the frequency of the high-frequency voltage is changed while keeping the amplitude thereof constant, to control the mass range of trappable ion. Thus, in terms of the amplitude of a high voltage to be applied to the ring electrode, the digital type requires a smaller value as compared with the analog type, which provides an advantage of being able to form a power supply circuit at low cost and avoid the occurrence of undesirable electrical discharge. Therefore, in principle, the digital type is free from restrictions on the mass range of trappable ions caused by electrical discharge in the analog type.
In cases where a sample is a biological sample, a laser desorption/ionization (LDI) source, such as a matrix-associated laser desorption/ionization (MALDI) source, is often used as the above ion source for producing ions to be trapped by the ion trap.
In an ion trap mass spectrometer comprising a combination of the MALDI source and the DIT, a sample is irradiated with a laser beam in pulsed form once and resulting ions arising from the sample are introduced into the ion trap. Then, after stably trapping the introduced ions within the ion trap, a part of the ions having a specific mass-to-charge ratio are oscillated and discharged from the ion trap, and the mass-separated ions are subjected to detection using the ion detector. A mass-to-charge ratio of oscillating ions is scanned to perform mass scanning, and a mass spectrum is created based on a detection signal obtained from the mass scanning.
However, the mass spectrum obtained by a single cycle of the above mass spectrometry analysis has a low S/N ratio, because the MALDI source is generally highly likely to fail to produce a sufficient amount of ions by one laser beam irradiation. Thus, the following cycle: ion production based on laser beam irradiation→ion introduction into the ion trap→ion trapping (cooling)→mass separation/detection, is repeated, and resulting mass profiles are subjected to an integration processing to provide an enhanced SN ratio. Although the number of the cycles may be increased to provide a more improved S/N ratio of the mass spectrum, a measurement time required for acquiring a measurement result, i.e., a final mass spectrum, will be increased to cause a problem about low throughput.
Particularly, in mass spectrometry imaging where a laser-beam irradiation position is scanned on a sample to perform two-dimensional mass spectrometry analysis, it is necessary to repeat the mass spectrometry analysis for a large number of measurement points. Thus, an improvement in the S/N ratio based in the above technique requires an awful lot of measurement time.
In the ion trap mass spectrometer configured to perform ionization under an atmospheric pressure using the MALDI source or the like, ions are introduced into the ion trap via the ion transport optical system based on the high-frequency electric field, as described above, wherein ions can be introduced into the ion trap after accumulating the ions in the ion transport optical system once. However, due to a mass dependence of ion transport efficiency in this type of ion transport optical system, there is another problem about limitation in a mass range of ions introduceable into the ion trap.
[Patent Document 1] JP 2003-512702A
[Non-Patent Document 1] Furuhashi, Takeshita, Ogawa, Iwamoto, “Development of Digital Ion Trap Mass Spectrometer”, Shimadzu Review, Shimadzu Review Editorial Department, Mar. 31, 2006, Vol. 62, No. 3·4, pp. 141-151